Anke Seydel
University of Padua
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Publication
Featured researches published by Anke Seydel.
Journal of Biomedical Science | 2017
Maria Rosaria Esposito; Sanja Aveic; Anke Seydel; Gian Paolo Tonini
Neuroblastoma is an embryonic malignancy of early childhood originating from neural crest cells and showing heterogeneous biological, morphological, genetic and clinical characteristics. The correct stratification of neuroblastoma patients within risk groups (low, intermediate, high and ultra-high) is critical for the adequate treatment of the patients.High-throughput technologies in the Omics disciplines are leading to significant insights into the molecular pathogenesis of neuroblastoma. Nonetheless, further study of Omics data is necessary to better characterise neuroblastoma tumour biology. In the present review, we report an update of compounds that are used in preclinical tests and/or in Phase I-II trials for neuroblastoma. Furthermore, we recapitulate a number of compounds targeting proteins associated to neuroblastoma: MYCN (direct and indirect inhibitors) and downstream targets, Trk, ALK and its downstream signalling pathways. In particular, for the latter, given the frequency of ALK gene deregulation in neuroblastoma patients, we discuss on second-generation ALK inhibitors in preclinical or clinical phases developed for the treatment of neuroblastoma patients resistant to crizotinib.We summarise how Omics drive clinical trials for neuroblastoma treatment and how much the research of biological targets is useful for personalised medicine. Finally, we give an overview of the most recent druggable targets selected by Omics investigation and discuss how the Omics results can provide us additional advantages for overcoming tumour drug resistance.
Oncotarget | 2016
Sanja Aveic; Marcella Pantile; Anke Seydel; Maria Rosaria Esposito; Carlo Zanon; Gary Li; Gian Paolo Tonini
Neuroblastoma (NB) is a threatening childhood malignancy. Its prognosis is affected by several morphological, and biological characteristics, including the constitutive expression of ALK tyrosine kinase. In this study we examined the therapeutic potential of a novel ALK inhibitor, entrectinib, in obliterating NB tumor cells. Entrectinib showed the growth-inhibitory effects on NB cells with a 50% inhibitory concentration range of 0.03–5 μM. In the ALK-dependent cells, entrectinib mediated G1-arrest, which was associated with modified expression of multiple cell-cycle regulators. Down-regulation of Ki-67, and attenuated phosphorylation of ERK1/2, and STAT3, correlated with observed antiproliferative capacity of entrectinib. Initial cytostatic activity of entrectinib was followed by concentration-dependent apoptotic cell death, and Caspase-3 activation. However, we delineated a reduced sensitivity of ALK mutated NB cells to entrectinib, and demonstrated strong activation of autophagy in SH-SY5YF1174L NB cell line. Abrogation of autophagy by chloroquine increased significantly the toxicity of entrectinib, as confirmed by enhanced death rate, and PARP protein cleavage in SH-SY5YF1174L cells. In aggregate, our data show that entrectinib inhibits proliferation, and induces G1-arrest, and apoptosis in NB cells. We propose entrectinib for further consideration in treatment of NB, and recommend pharmacological inhibition of autophagy to be explored for a combined therapeutic approach in NB patients that might develop resistance to entrectinib.
Protein Expression and Purification | 2008
Elisa Pasqualetto; Anke Seydel; Alberto Pellini; Roberto Battistutta
The membrane protein prestin is the voltage-sensitive molecular motor underlying somatic electromotility of outer hair cells. In order to produce adequate quantities to perform structural and functional studies, we cloned and expressed in bacterial systems three variants of the cytosolic C-terminal STAS domain of prestin from Rattus norvegicus. While the expression level of the longer form of the C-terminal domain (fragment [505-744]) was very low or absent, we succeeded in the overexpression of two shorter fragment of the STAS domain (fragments [529-744], PreCD(L), and [529-720], PreCD(S)). These two polypeptides were purified to homogeneity and characterised by circular dichroism, fluorescence spectroscopy and dynamic light scattering. The two proteins possess a three-dimensional structure and show a great tendency to aggregate. In particular, PreCD(L) is present in solution mainly as dimers and tetramers. These data correlate with that of full-length prestin that forms stable tetramers, suggesting that the C-terminal domain play an important role in modulating the properties of the entire prestin.
Biochimica et Biophysica Acta | 2008
Luciana Esposito; Anke Seydel; Rosa Aiello; Giosué Sorrentino; Laura Cendron; Giuseppe Zanotti; Adriana Zagari
Superoxide dismutases (SODs) are key enzymes for fighting oxidative stress. Helicobacter pylori produces a single SOD (HpSOD) which contains iron. The structure of this antioxidant protein has been determined at 2.4 A resolution. It is a dimer of two identical subunits with one iron ion per monomer. The protein shares 53% sequence identity with the corresponding enzyme from Escherichia coli. The model is compared with those of other dimeric Fe-containing SODs. HpSOD shows significant differences in relation to other SODs, the most important being an extended C-terminal tail. This structure provides a model for closely related sequences from species such as Campylobacter, where no structures are currently known. The structure of extended carboxyl termini is discussed in light of putative functions it may serve.
Infection and Immunity | 2002
Anke Seydel; Elisabetta Tasca; Duccio Berti; Rino Rappuoli; Giuseppe Del Giudice; Cesare Montecucco
ABSTRACT Helicobacter pylori infection causes severe gastroduodenal diseases in humans. Its virulence is strongly increased by the presence of the cag pathogenicity island (cag PAI). It has been shown that CagA, a major antigen in humans, is translocated to the host cell via a secretion system encoded by the cag PAI. The roles of many of the proteins encoded within the cag PAI are not known. Here we report on the cloning and expression of CagF, one of those proteins. We show that CagF is associated to the outer membrane of H. pylori G27 and that the protein is always expressed with electrophoretic mobility variations among the 20 strains tested here. We have also found that natural infection with H. pylori is able to induce antibodies against CagF.
Proteins | 2007
Laura Cendron; Elisabetta Tasca; Tommaso Seraglio; Anke Seydel; Alessandro Angelini; Roberto Battistutta; Cesare Montecucco; Giuseppe Zanotti
The crystal structure of CagS from the Helicobacter pylori pathogenicity island Laura Cendron, Elisabetta Tasca, Tommaso Seraglio, Anke Seydel, Alessandro Angelini, Roberto Battistutta, Cesare Montecucco, and Giuseppe Zanotti* 1Department of Chemistry, University of Padua, and Institute of Biomolecular Chemistry, CNR Padua, Via Marzolo 1, 35131 Padua, Italy 2 Venetian Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padua, Italy 3Department of Medical Science, CNR Centre of Biomembranes, University of Padua, Via G. Colombo 3, 35121 Padua, Italy
Microbial Cell Factories | 2006
Alessandro Angelini; Laura Cendron; Anke Seydel; Nicola Barison; Tommaso Tosi; Roberto Battistutta; Giuseppe Zanotti
Helicobacter pylori chronically infects the gastric mucosa of millions of people annually worldwide: it has been estimated that over 50% of the world population carries this infection. H. pylori has been associated with the development of several diseases, like chronic gastritis, gastric and duodenal ulcer, gastric adenocarcinoma and mucosa-associated lymphoma [1-3]. The complete genome sequence of two different isolates of H. pylori (J99 and 26995) is known. The strains that contain a 37 kb foreign DNA region, called cag pathogenicity island (cag-PAI), cause the most severe form of virulence [4]. The cag-PAI encodes for a functional type IV secretion apparatus homologous to the VirB/D4 Type IV Secretion System (T4SS) of the plant pathogen Agrobacterium tumefaciens and other Gram-negative bacteria [5]. T4SSs are involved in conjugal DNA transfer, in the DNA delivery to (or uptake from) the environment, for instance the release of oncogenic DNA into infected plant cells by A. tumefaciens, or in the translocation of effector proteins [6,7]. The T4SS encoded by the cag-PAI of H. pylori is responsible for the translocation into the host cell of the protein CagA, a major antigenic virulence factor encoded within the cag-PAI. Once secreted into the gastric epithelial cells, CagA induces cellular modifications, such as elongation and spreading of host cells [8]. The aim of this structural genomic project is to determine the three-dimensional structure of most of the proteins encoded by the cag-PAI, a task that will allow to elucidate the function and the organization of the entire T4SS of such a relevant pathogenic bacterium [9].
Acta Crystallographica Section A | 2005
Giuseppe Zanotti; Laura Cendron; Anke Seydel; Alessadnro Angelini; Roberto Battistutta
H. pilory is a Gram-negative bacterium that colonizes the stomach of probably half of the human population. It is associated with gastritis, peptic ulcers and mucosa-associated lymphoid tissue lymphomas. Many factors contribute to the virulence of H. pylori [1]. Among them, the enzyme urease, the Neutrophil Activating Protein, NAP [2] and the secreted protein toxin VacA. However, the major genetic difference in HP isolates is the presence or absence of a specific pathogenicity island, named cag-PAI. It is a 40-kb locus that contains about 30 ORFs, whose function is unknown, with few exceptions. We have cloned, expressed, and purified several proteins of the cag pathogenicity island of H. pylori. They all have been expressed in E. coli. We have already solved the structure of CagZ, using the SeMet method [3] and the structure will be described in detail. We have also obtained crystals of a second protein, CagS, and its structure determination is in progress, along with crystallization tests on other cag proteins. Our final goal is to determine, in collaboration with other groups [4], most of the proteins coded by the cag-PAI island.
Journal of Molecular Biology | 2004
Laura Cendron; Anke Seydel; Alessandro Angelini; Roberto Battistutta; Giuseppe Zanotti
Advances in Modern Oncology Research | 2016
Maria Rosaria Esposito; Sanja Aveic; Anke Seydel; Gian Paolo Tonini